Markers map slide into Alzheimer's

Researchers from Washington University School of Medicine in St. Louis and the Dominantly Inherited Alzheimer Network (DIAN) have used biomarkers to tag the cognitive decline into full-blown Alzheimer's disease. This is the most detailed chronology to date, according to the researchers, and could show that the disease could begin 25 years before symptoms show themselves. This knowledge could be used to track and treat this hereditary form of the disease, as well as to help researchers learn more about the much more common sporadic form.

Autosomal dominant Alzheimer's disease is an inherited form, and symptoms begin around a predictable age, often in the 30s or 40s. The researchers looked at data from 128 people with this form of the disease, including clinical and cognitive status, brain imaging and results from blood and cerebrospinal fluid (CSF) tests. They found that the concentration of amyloid beta in the CSF started to fall 25 years before symptoms would be expected to begin (based on their parents' age of disease onset), and the start of amyloid beta plaque formation began around 15 years before expected symptom onset, around the same time as increases in brain atrophy and tau protein concentration in the CSF. Other markers could also be added to the timeline.

Dealing with Alzheimer's disease is a big and growing issue--it's the most common cause of dementia, affecting around 5 million people in the U.S., potentially increasing to 13 million by 2050. Knowing the timescale of disease development could help drug developers and doctors know when best to schedule clinical trials or treatment, for example drugs that are intended to block or reduce plaque formation may work best more than a decade before symptoms are seen. These markers could also be used to track the efficacy of treatment, as surrogate markers of the full-blown disease.

The research is interesting, as Laurie Ryan, clinical trials program director at the National Institute on Aging, says: "These exciting findings are the first to confirm what we have long suspected, that disease onset begins years before the first sign of cognitive decline or memory loss. And while DIAN participants are at risk for the rare, genetic form of the disease, insights gained from the study will greatly inform our understanding of late-onset Alzheimer's disease."

However, others are somewhat more skeptical. Dr. Ronald Petersen of the Mayo Clinic said to MedPage Today: "Very interesting data but more useful for hypothesis generation than having direct implications at present. This may be an unusual form of the Alzheimer's disease process and not generalizable to the disease as it exists in the community."

- read the press release
- see the paper in the NEJM
- check out the article in Technology Review
- get the article in MedPage Today